Gout

Objectives
To review the etiology and
pathophysiology of gout
To recognize predisposing factors for gout
To review diagnostic criteria and
evaluation for gout
To know the appropriate treatment for
acute and chronic gout

What is Gout?
Marked by recurrent attacks of acute inflammatory
arthritis
Disease of kings or rich mans disease
Characterized by an abnormal metabolism of uric acid hyperuricemia
Overload of uric acid in the body which subsequently
deposited in the tissues of body.
Crystals of uric acid deposited in joint tissues will cause
joint inflammation (arthritis)
Repeated attacks of gouty arthritis can damage the joint
and lead to chronic arthritis.

Signs & Symptoms

Most common site for gout is the small joint at the base of
the big toe (75%). When this happens it is known as
podagra.
Also affect other joints e.g. ankles, knees, wrists, fingers &
elbows
Acute attack is characterized by a rapid onset of pain in the
affected joint, followed by warmth, swelling, redness &
tenderness
1st attack can subside spontaneously after 1 or 2 weeks
With time, attacks can occur more frequently & may last
longer in the same joint or in another joint
Collection of uric acid crystals outside joints form tophi
which can be seen e.g. in elbows, fingers etc

URATE, HYPERURICEMIA &

GOUT
Urate: end product of purine metabolism
Hyperuricemia: serum urate > urate solubility (>
6.8 mg/dl)
Gout: deposition of monosodium urate crystals
in tissues

HYPERURICEMIA & GOUT

Hyperuricemia caused by
Overproduction
Underexcretion
No Gout w/o crystal deposition

Classification of Hyperuricemia

Uric acid overproduction

Accounts for 10% of hyperuricemia
Defined as 800mg of uric acid excreted
Acquired disorders
Excessive cell turnover rates such as myleoproliferative disorders, Pagets
disease, hemolytic anemias

Genetic disorders: derangements in mechanisms that regulate purine

neucleotide synthesis.

Uric acid underexcretion

Accounts for >90% of hyperuricemia
Diminished tubular secretory rate, increased tubular reabsorption,
diminished uric acid filtration
Drugs, other systemic disease that predispose people to renal insufficiency

Pathogenesis of Gouty Inflammation

Urate crystals stimulate the release of numerous
inflammatory mediators in synovial cells and
phagocytes
The influx of neutrophils is an important event for
developing acute crystal induced synovitis
Chronic gouty inflammation associated with
cytokine driven synovial proliferation, cartilage
loss and bone erosion

Prevalence of Gout

5x more common in men than in pre-menopausal women.

In male onset of gout usually after puberty.
In women gout usually occurs after menopause.
After age 60 incidence almost same as men.
If your parents have gout, you have 20% chance of
developing it.
Not all people with elevated serum uric acid will have
gout. Only 10% of people with hyperuricemia develop
gout.
People with long standing hyperuricemia can form tophi
(uric acid crystals deposit) in tissue.

GOUT: A Chronic Disease of 4

stages
Asymptomatic hyperuricemia
Acute Flares of crystallization
Intervals between flares
Advanced Gout & Complications

ACUTE GOUTY FLARES

Abrupt onset of severe joint inflammation,
often nocturnal;
Warmth, swelling, erythema, & pain;
Possibly fever
Untreated? Resolves in 3-10 days
90% 1st attacks are monoarticular
50% are podagra

SITES OF ACUTE FLARES

90% of gout patients
eventually have
podagra : 1st MTP
joint

INTERVALS SANS FLARES

Asymptomatic
If untreated, may advance
Intervals may shorten
Crystals in asymptomatic joints
Body urate stores increase

FLARE INTERVALS
Silent tissue
deposition & Hidden
Damage

ADVANCED/ CHRONIC GOUT

Chronic Arthritis
X-ray Changes
Tophi Develop
Acute Flares continue

ADVANCED GOUT
Chronic Arthritis
Polyarticular acute
flares with upper
extremities more
involved

TOPHI
Solid urate deposits in
tissues

TOPHI RISK FACTORS

Long duration of hyperuricemia
Higher serum urate
Long periods of active, untreated gout

Complications of Gout
Renal Failure
ARF can be caused by
hyperuricemia, chronic
urate nephropathy

Nephrolithiasis
Joint deformity
Recurrent Gout

GOUT RISK FACTORS

Male
Postmenopausal female
Advancing age
Hypertension
Pharmaceuticals:
Diuretics, Aspirin,
cyclosporine, nicotinic
acid, cytotoxics
Hereditary 20% chance
if parents have
hypothyroidism

GOUT RISK FACTORS

Alcohol intake
Highest with beer
Not increased with wine
High BMI (obesity)
Diet high in meat, seafood, internal organs, yeast, oily
fish
Abnormal kidney function
Rapid turnover of cells- e.g. psoriasis & tumour
Lead poisoning
Starvation & dehydration

Diagnosis
Most reliable test is detecting uric acid in joint
fluid obtained by joint aspiration(arthrocentesis)
Bright needle- like uric acid crystals can be
seen in the joint fluid under polarized
microscope
Blood test uric acid levels, kidney function
X-rays can show joint damage esp in patients
who have multiple episodes of gouty arthritis

Treatment Goals
Gout can be treated without complications.
Therapeutic goals include
terminating attacks
providing control of pain and inflammation
preventing future attacks
preventing complications such as renal
stones, tophi, and destructive arthropathy

Non- Pharmacologic Treatments

Immobilization of Joint
Ice Packs
Abstinence of Alcohol
Consumption can increase serum urate levels by
increasing uric acid production. When used in excess
it can be converted to lactic acid which inhibits uric
acid excretion in the kidney

Dietary modification
Low carbohydrates
Increase in protein and unsaturated fats
Decrease in dietary purine-meat and seafood. Dairy
and vegetables do not seem to affect uric acid

Pharmacologic Treatment For Gout

Can be divided into :
1) Acute Gout Treatment
2) Chronic Gout Treatment

Acute Gout treatment

Agents : A) NSAIDs
B) Corticosteroids
C) Colchicine
Do not start a urate lowering agent(e.g. allopurinol)
during an acute attack
If patient on urate lowering agent, do not stop or adjust
dose

Colchicine
Must be started in 1st 24 hour
Narrow therapeutic-toxic ratio GI upset in 80% including nausea, diarrhoea,or abdominal cramps
Limited therapeutic use in acute gout
Other S/E bone marrow suppression,renal failure,
congestive heart failure,death
Adm orally in hourly dose of 0.5mg to 0.6mg until pain &
inflammation resolved or until max dose 0f 6mg/24hr
Or 2mg IV then 0.5mg q6H until cumulative dose of 4mg
over 24 hours

Colchicine - continue
Not effective late in flare
For healthy adults only
Should not be used by elderly patients or those with
kidney, liver or bone marrow disorders, pregnancy
Erythromycin & H2 blockers ( cimetidine, famotidine &
ranitidine) may intensify GI S/E of colchicine
Long term colchicine therapy may also weaken the
respiratory muscles, esp in renal patients

Non steroidal Anti-inflammatory

Drugs
Used in patient without contraindication e.g. peptic
ulcer, warfarin
Need max dose/potent NSAIDs
E.g. Indomethacine 50mg tid
Diclofenac 50mg tid
Meloxicam 7.5mg daily
Celecoxib 200mg daily or bd
Continue until pain/inflammation absent for 48 hours
NSAIDs will be covered in Topic 2 Rheumatoid arthritis

Corticosteroid
Used when NSAIDs risky or contraindicated
e.g. elderly
- renal impairment
- liver impairment
Used when NSAIDs ineffective
Mode of adm i) intra-articular with drainage (risk of sepsis)
eg Triamcinolone 10-40mg or
Dexamethasone 2-10mg alone or
with lignocaine
ii) oral prednisolone 40-60mg daily for 3-4
days. Then taper by 5mg every 2-3 days
Improvement seen in 12-24 hours

Urate Lowering Treatment

(Chronic Gout Treatment)

NEVER start a uric acid lowering agent during an acute

attack
Halt crystal formationcure the disease
Asymptomatic hyperuricemia is not an indication for
treatment
Who to treat? (Indication)
i) tophi or chronic arthritis
ii) failure of colchicine prophylaxis
iii) radiographic changes of gout
iv) multiple joint involvement
v) nephrolithiasis (renal stones)
vi) extremely high levels of serum uric acid (>12mg/dl)

Agents That Reduces Uric Acid

Synthesis
Allopurinol (Zyloric )
An inhibitor of xanthine oxidase, an enzyme which
converts purine (from DNA breakdown) into uric acid
Taken orally start low e.g. 50-100mg daily
by 50-100mg every 2-3 days according to symptoms
Average dose : 300mg daily
- lower dose if renal/hepatic insufficiency
- higher dose in non-responders
In divided doses if more than 300mg/day
Prophylactic colchicine until allopurinol dose stable

Allopurinol - continued
S/E : headache, dyspepsia, diarrhea, rash,
drug interactions, acute exacerbation of
gout initially
Rarely life threatening hypersensitivity
Drug interaction with coumadin(warfarin)
- cyclosporin
- azathioprine
Allopurinol may prolong half-life of these
drugs & increase toxicity

Agents That Increase Uric Acid Excretion

These are called uricosurics
E.g. of uricosurics include sulfinpyrazone and probenecid
MOA : compete with uric acid for reabsorption in the proximal
tubules, preventing uric acid reabsorption and resulting in
uricosuria
Uricosurics are usually choice for preventing gout in the
following patients:
- those less than 60 years old
- those with normal diets 24 hours
- those with normal kidney function
- those who have no risk o kidney stones
- those who excrete less than 700mg of uric acid over

URICOSURICS
PROBENECID ( Benemid )

ROA : oral
Dose :
- 250mg bd for 1 week then followed by 500mg bd
- best taken with food or milk to prevent GI S/E
- drink lots of fluid prevent formation of kidney stones
- avoid large doses of vit c risk of kidney stones
S/E : LOA, drowsiness, vomiting, headache, sore gum & frequent
urination

Drug Interactions of Probenecid

Salicylates & aspirin can effectiveness of
probenecid
Probenecid can prolong or enhance the action of
sulfonylureas - hypoglycemia
half-life of some NSAIDs
plasma concentration of methotrexate
Prolong ketamine & thiopental anaesthesia

URICOSURICS
Sulfinpyrazone ( Anturan )
ROA : oral
Dose :
100-200mg daily with food or milk
increasing 2-3 week to 600mg daily in 2 divided doses

S/E : GI upset, LOA, drowsiness, blood dyscrasias, kidney stones,

and acute exacerbation of gout initially, hypersensitivity
reactions(rash)
Should not be used for acute gout

Drug Interactions Of Sulfinpyrazone

May effects of these drugs
warfarinbleeding
tolbutamide blood sugar
May the effects of these drugs
theophylline worsening of asthma
verapamil worsening of heart problem
May hepatotoxicity of paracetamol

Gout Prophylaxis
Colchicine (at low dose)
Indication:
- until dose of urate lowering drug optimized
- If pt cannot take a urate lowering drug
Dose:
- 0.6mg qd or occasionally bid
- 0.3mg qd or q2days if renal dx or elderly
SMALLEST DAILY DOSE POSSIBLE
INDIVIDUALISE